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QUININE SULPHATE TABLETS BP 300 MG

Active substance: QUININE SULPHATE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Quinine Sulphate Tablets BP 300mg.

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains quinine sulphate BP 300mg.

3

PHARMACEUTICAL FORM
Coated tablet.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
For the treatment of chloroquine-resistant strains of falciparium malaria.
Treatment and prevention of nocturnal leg cramps in adults and the elderly,
when cramps cause regular disruption of sleep (see section 4.2 and section
4.4)

4.2

Posology and method of administration
Treatment of chloroquine-resistant strains of falciparium malaria:
Adults:
600mg every 8 hours for 7 days, followed by (or with) an appropriate dose of
a sulphadoxine/pyrimethamine combination, such as Fansidar.
Elderly:
There is no evidence that the dosage should differ in the elderly.
Children:
Not recommended.
For the treatment and prevention of nocturnal leg cramps:
Adults (including elderly):
The recommended dose is 200mg at bedtime. The maximum dose is 300mg.
A reduction in frequency of leg cramp may take up to 4 weeks to become
apparent. Patient should be monitored closely during the early stages of
treatment for adverse effects. After an initial trial of 4 weeks, treatment should
be stopped if there is no benefit. Treatment should be interrupted at
approximately three monthly intervals to reassess the benefit of treatment.

4.3

Contraindications
Haemoglobinuria
Known hypersensitivity to quinine or any of the excipients in the tablet
Optic neuritis
Tinnitus
Myasthenia gravis

4.4

Special warnings and precautions for use
Administration of quinine may give rise to cinchonism, which is generally more
severe in overdose, but may also occur in normal therapeutic doses. Patients should
be warned not to exceed the prescribed dose, because of the possibility of serious,
irreversible side effects in overdose. Treatment for night cramps should be stopped if
symptoms of cinchonism emerge. Such symptoms include tinnitus, impaired hearing,
headache, nausea, and disturbed vision (see sections 4.8 and 4.9)
Before use for nocturnal leg cramps, the risks, which include significant adverse
effects and interactions ( see sections 4.5 and 4.8), should be carefully considered
relative to the potential benefits. These risks are likely to be of particular concern in
the elderly. Quinine should only be considered when cramps are very painful or
frequent, when other treatable causes of cramp have been ruled out, and when nonpharmacological measures have not worked. Quinine sulphate should not be used for
this indication during pregnancy (see section 4.6).
Quinine may cause unpredictable serious and life-threatening thrombocytopenia,
which is thought to be an idiosyncratic hypersensitivity reaction. Quinine should not
be prescribed or administered to patients who have previously experienced any
adverse reaction to quinine, including that in tonic water or other beverages. Patients
should be instructed to stop treatment and consult a physician if signs of
thrombocytopenia such as unexplained bruising or bleeding occur.
Quinine should be used with caution in patients with atrial fibrillation or other serious
heart disease. It may cause hypoprothrombinaemia.
Patients with glucose 6-phophate dehydrogenase (G6PD) deficiency may develop
acute haemolytic anaemia.
Hypersensitivity to quinine may also occur with symptoms of cinchonism together
with urticaria, flushing, puritus, rash, fever, angioedema, dyspnoea and asthma.
The administration of quinine to a patient who has previously been suffering from a
chronic and inadequately controlled malarial infection may precipitate an attack of
blackwater fever. However, in some cases deficiency of glucose-6-phosphate
dehydrogenase may have been involved. Glucose-6-phosphate dehydrogenase
deficient patients with malaria or taking quinine to treat leg cramps may be at an
increased risk of haemolytic anaemia during quinine therapy.
Quinine should not be withheld from pregnant women who have life threatening
malaria (see section 4.6).
Treatment with quinine should be monitored in case signs of resistance develop.

4.5

Interaction with other medicinal products and other forms of interaction
Effect of other drugs on quinine
Quinine is metabolised via hepatic oxidative cytochrome P450 pathways,
predominantly by CYP3A4.
There is the potential for increased quinine toxicity with concurrent use of potent
CYP3A4 inhibitors, which include azole antifungal drugs and HIV protease
inhibitors.
Sub-optimal quinine serum levels may result from concomitant use of CYP3A4
inducers, which include rifampicin, barbiturates, carbamazepine and phenytoin.
Care should be taken when quinine is used in combination with other CYP3A4
substrates, especially those causing prolongation of the QT interval.
Effect of quinine on other drugs
The plasma concentration of flecainide, digoxin and mefloquine may be increased.
Amantadine: Quinine can reduce the renal clearance of amantadine.
Ciclosporin: Quinine can decrease plasma concentrations of ciclosporin.
Cardiac glycosides: Quinine increases plasma concentrations of cardiac glycosides
and reduced dosage of concomitant cardiac glycosides such as digoxin to half the
maintenance dose may be necessary.
Other drug interactions
There is an increased risk of ventricular arrhythmias with other drugs which prolong
the QT interval, including amiodarone, moxifloxacin, pimozide, thioridazine and
halofantrine.
Antiarrhythmics: Concomitant use of amiodarone should be avoided due to the
increased risk of ventricular arrhythmias. The plasma concentration of flecainide is
increased by quinine. Concomitant use of quinidine may increase the possibility of
cinchonism.
Antibacterials: There is an increased risk of ventricular arrhythmias when
moxifloxacin is given with quinine. Rifampicin can reduced the serum levels of
quinine, therefore reducing its therapeutic effect.
Anticoagulants: Quinine may cause hypoprothrombinaemia and enhance the effects
of anticoagulants.
Antihistamines: Concomitant use of terfenadine should be avoided due to the
increased risk of ventricular arrhythmias.
Antimalarials: According to the manufacturer of artemether with lumefantrine
concomitant use should be avoided. There is an increased risk of convulsions when
given with mefloquine. Chloroquine and quinine appear to be antagonistic when
given together for P falciparum malaria. There is a decrease in plasma concentrations
of primaquine.
Antipsychotics: There is an increased risk of ventricular arrhythmias and concomitant
use should be avoided with pimozide or thioridazine.
Hypoglycaemics: Concurrent use with oral hypoglycaemics may increase the risk of
hypoglycaemia .
Suxamethonium: Quinine enhances the neuromuscular effects of suxamethonium.

Ulcer-healing drugs: Cimetidine inhibits quinine metabolism leading to increased
plasma-quinine concentrations.

4.6

Fertility, Pregnancy and lactation
Pregnancy
Quinine may cause congenital abnormalities of the CNS and extremities.
Following administration of large doses during pregnancy, phototoxicity and
deafness have been reported in neonates. Quinine sulphate should not be used
during pregnancy unless the benefits outweigh the risks.
Treatment of chloroquine-resistant strains of falciparium malaria.
Pregnancy in a patient with malaria is not generally regarded as a contraindication to the use of quinine. As malaria infection is potentially serious
during pregnancy and poses a threat to the mother and foetus, there appears to
be little justification in withholding treatment in the absence of a suitable
alternative.
Prophylaxis of nocturnal leg-cramps.
Quinine sulphate should not be used during pregnancy to treat cramps.
Lactation
Quinine sulphate is excreted in breast milk, but no problems in humans have
been reported. However, quinine sulphate should not be given to nursing
mothers unless the benefits outweigh the risks.

4.7

Effects on ability to drive and use machines
Quinine may cause visual disturbances and vertigo, hence patients should be advised that if
affected they should not drive or operate machinery.

4.8

Undesirable effects
Cinchonism is more common in overdose, but may occur even after normal doses of
quinine. In its mild form symptoms include tinnitus, impaired hearing, rashes,
headache, nausea and disturbed vision. Its more severe manifestations symptoms may
include gastrointestinal symptoms, oculotoxicity, CNS disturbances, cardiotoxicity
and death (see section 4.9). Visual disorders may include blurred vision, defective
colour perception, visual field constriction and total blindness.
MedDRA system organ class
Blood and lymphatic system disorders

Adverse Reaction
Thrombocytopenia, intravascular coagulation,
hypoprothrombinaemia, haemoglobinuria, oliguria,
haemolytic-uremic syndrome, pancytopenia,
haemolysis, agranulocytosis, thrombocytopenic

purpura
Immune system disorders

Metabolism and nutrition disorders

Psychiatric disorders
Nervous system disorders
Eye disorders
Ear and labyrinth disorders
Cardiac disorders

Respiratory, thoracic and mediastinal
disorders
Gastrointestinal disorders
Skin and subcutaneous tissue disorders

Musculoskeletal and connective tissue
disorders
Renal and urinary disorders

Reproductive system and breast
disorders

4.9

Reports have been received of eczematous
dermatitis, oedema, erythema and lichen planus.
Hypersensitivity reactions such as asthma,
angioneurotic oedema, photosensitivity, hot and
flushed skin, fever, pruritis, thrombocytopenic
purpura and urticaria have also been reported
Hypoglycaemia may occur after oral administration
although it is more common after parenteral
administration
Agitation, confusion
Headache, vertigo, excitement, loss of
consciousness, coma and death have been reveived.
Blurred vision, defective colour perception, visual
field constriction
Tinnitus, impaired hearing
Atrioventricular conduction disturbances,
hypotension coupled with a feeble pulse,
prolongation of the QT interval, widening of the
QRS complex and T wave flattening
Bronchospasm, dyspnoea may occur
Nausea, vomiting, diarrhoea, abdominal pain may
occur after long term administration of quinine
Flushing, rash, urticaria, eczematous dermatitis,
oedema, erythema, lichen planus, pruritis,
photosensitivity
Muscle weakness, aggravation of myasthenia gravis
Renal insufficiency and acute renal failure may be
due to an immune mechanism or to circulatory
failure.
Toxic doses of quinine may induce abortion, but it is
unwise to withhold the drug if less toxic
antimalarials are not available

Overdose
Quinine overdosage may lead to serious side effects including irreversible visual loss
, and can be fatal. In acute overdosage, symptoms of cinchonism may occur,
including nausea, vomiting, tinnitus, deafness, headache, vasodilation and visual
disturbance.
Features of a significant overdose include convulsions, impairment of consciousness,
coma, respiratory depression, QT prolongation, ventricular arrhythmia, cardiogenic
shock and renal failure. Fatalities have been reported in adults after doses of 2-8g.
High doses of quinine are tetrogenic and may cause miscarriage. Hypokalaemia and
hypoglycaemia may also occur.
Treatment
Children (< 5 years) who have ingested any amount should be referred to hospital.

Older children and adults should be referred to hospital if more than 30 mg/kg of
quinine base has been taken.
Each that each 200 mg tablet is equivalent to 165 mg quinine base/each 300 mg tablet
is equivalent to 248 mg quinine base.
Quinine is rapidly absorbed. Consider activated charcoal (50 g for adults; 1 g/kg for
children) if the patient presents within 1 hour of ingestion of more than 30 mg/kg
quinine base or any amount in a child under 5 years. Multiple dose activated charcoal
will enhance quinine elimination.
Observe patients for at least 12 hours after ingestion. Monitor cardiac conduction and
rhythm, serum electrolytes, blood glucose and visual acuity.
Other treatment is symptomatic to maintain blood pressure, respiration, renal function
and to treat arrhythmia, convulsions, hypoglycaemia and acidosis.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
ATC Code: P01B C01. Quinine alkaloid.
Quinine is a cinchona alkaloid and a 4-methanolquinoline antimalarial agent which is
a rapidly acting blood schizontocide with activity against Plasmodium faciparum, P
vivax, P ovale and P malariae. It is active against the gametocytes of P malariae and
P vivax, but not against mature gametocytes of P falciparum. Since it has no activity
against exoerythrocytic forms, quinine does not produce a radical cure in vivax or
ovale malarias.
Quinine has effects on the motor end-plate of skeletal muscle and prolongs the
refractory period. Like quinidine, quinine is a sodium channel blocker and, therefore,
has local anaesthetic, and both anti- and proarrhythmic activity.
The precise mechanism of action of quinine is unclear but it may interfere with
lysosome function or nucleic acid synthesis in the malaria parasite.

5.2

Pharmacokinetic properties
The pharmacokinetics of quinine are altered significantly by malaria infection, the
major effects being reductions in both its apparent volume of distribution and its
clearance.

Absorption: Quinine is rapidly and almost completely absorbed from the GI tract and
peak concentrations in the circulation are attained about 1-3 hours after oral
administration of the sulphate.
Distribution: Plasma protein binding is about 70% in healthy subjects and rises to
90% or more in patients with malaria.
Quinine is widely distributed throughout the body. Concentrations attained in the CSF
of patients with cerebral malaria have been reported to be about 2-7% of those in the
plasma.
Metabolism: Quinine is extensively metabolised in the liver and rapidly excreted
mainly in the urine. Estimates of the proportion of unchanged quinine excreted in the
urine vary from less than 5% to 20%. The pharmacokinetics of quinine are altered
significantly by malaria infection, with reductions in both the apparent volume of
distribution and clearance.
Elimination: Excretion is increased in acid urine. The elimination half-life is about 11
hours in healthy subjects but may be prolonged in patients with malaria. Small
amounts of quinine also appear in the bile and saliva.
Quinine crosses the placenta and is excreted in the breast milk.

5.3

Preclinical safety data
Not required.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose, maize starch, magnesium stearate, stearic acid, talc, sodium
croscarmellose, opaglos, sucrose and titanium dioxide (E171).

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
36 months.

6.4

Special precautions for storage
Store in a cool dry place and protect from light.

6.5

Nature and contents of container
Securitainers and opaque screw-capped plastic containers.
Pack sizes: 25, 50, 100 and 500.
Lever-lid tins (polybag lined). Pack size: 1,000.
Ward packs. Pack size: 100.

6.6

Special precautions for disposal
Not applicable.

7

MARKETING AUTHORISATION HOLDER
Ennogen Pharma Limited
Unit G4,
Riverside Industrial Estate,
Riverside Way,
Dartford
DA1 5BS
UK

8

MARKETING AUTHORISATION NUMBER(S)
PL 40147/0071

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
9 April 1992

10

DATE OF REVISION OF THE TEXT
08/01/2013

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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